As a method for producing an optically active benzhydrol, which is one of optically active alcohols, a lot of cases have already been reported. For example, there has been a known method of conducting an asymmetric reduction of asymmetrical benzophenones, and typical examples are as follows.
(1) Patent Document 1 discloses a method of conducting an asymmetric hydrogenation reaction of asymmetrical benzophenones using an optically active ruthenium complex as a catalyst.
(2) Patent Document 2 discloses a method of conducting an asymmetric reduction of asymmetrical benzophenones with sodium borohydride using an optically active cobalt complex as a catalyst.
However, in these methods, when a substituent is not present at the ortho position of at least one aromatic ring of raw material asymmetrical benzophenones, it has been impossible to produce benzhydrols having a high optical purity, and the substrate generality has been poor.
Meanwhile, as a method for producing an optically active benzhydrol from an aromatic aldehyde and an aryl metal compound, some cases have been known.
(3) Patent Document 3 discloses a method of reacting a diaryl zinc compound with an aromatic aldehyde in the presence of a catalytic amount of an optically active amino alcohol.
(4) Non-Patent Document 1 discloses a method of reacting a triarylaluminum compound with an aromatic aldehyde in the presence of tetra-iso-propoxy titanium and a catalytic amount of an optically active biphenol compound.
(5) Non-Patent Document 2 discloses a method of reacting an aryltitanium compound with an aromatic aldehyde in the presence of a catalytic amount of an optically active Tadol titanium complex.
(6) Non-Patent Document 3 discloses a method of reacting an arylmagnesium compound with an aromatic aldehyde in the presence of a tetra-iso-propoxy titanium compound and a catalytic amount of an optically active binaphthyl compound.
(7) Non-Patent Document 4 discloses a method of reacting an optically active aryltitanium compound derived from an optically active binaphthol with an aromatic aldehyde.
In the methods of (3) and (4), an aryl metal compound in an excessive amount relative to the aldehyde is needed, which is not practical particularly when addition of a complex aromatic compound is desired. Furthermore, these aryl metal compounds are highly reactive and unstable, but in order to achieve high enantioselectivity, the aryl metal compound needs to be isolated. In the method (5), in order to carry out the reaction using an aryltitanium compound, the amount of the aryltitanium compound is close to 1 equivalent relative to the aldehyde and the reaction proceeds quantitatively. However, the aryltitanium compound needs to be isolated, and in order to achieve high enantioselectivity, the reaction temperature needs to be a lower temperature. In the method (6), a large excess amount (5.8 equivalents) of tetra-iso-propoxy titanium is needed. Furthermore, with regard to synthesis of benzhydrols, enantioselectivity is not sufficient either. In the method (7), equal to or more than 1 equivalent of an optically active binaphthol is needed.
As described above, a method for producing an optically active alcohol combined with industrially desirable conditions, particularly an optically active benzhydrol, has not been known.